CompArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors (LINEAR)

February 17, 2026 updated by: European Institute of Oncology

CLINical, Pathological and outcomE compArative Analysis Between, Thymic, pulmonaRy and Pancreatic Well Differentiated High Grade Neuroendocrine Tumors: a Retrospective Observational Study

The study involves the enrollment of 34 patients diagnosed with advanced thymic, pulmonary and duodeno-pancreatic well-differentiated high grade neuroendocrine tumors (Ki-67 > 20%). The objective of this retrospective single-centre translational study will be to explore whether patients differ clinically in terms of diagnosis and treatment management. Currently, well differentiated high grade pulmonary NETs are managed using extrapolated algorithms from duodeno-pancreatic NETs, underlining a significant unmet clinical need. This is likely due to the rarity, uncertain pathological and molecular classification, and heterogeneous clinical course of well differentiated high grade pulmonary NETs.

In this study a retrospective data-base of pulmonary, thymic and duodeno-pancreatic NETs with Ki-67 > 20% will be created in order to analyze diagnostic and therapeutic pathways, clinical outcomes, imaging, disease evolution and molecular profiling. This study will adopt a hypothesis-generating approach to explore whether patients in these distinct groups differ clinically in terms of diagnosis and treatment management.

Study Overview

Status

Recruiting

Conditions

Detailed Description

The LINEAR study aims to address unmet medical clinical needs in LNETs. This project specifically focuses on lung and thymic advanced NETs with Ki-67 > 20%, a rare subtype of lung cancer subtypes characterized by heterogeneous biological behaviour and variable clinical course. This contrasts with duodeno-pancreatic NETs, for which a higher level of evidence currently guides treatment sequencing. The molecular landscape and optimal therapeutic strategies for thymic and LNETs remain under investigation and are currently based on pathological features and metabolic imaging findings. Some LNETS present a carcinoids morphology but exhibit elevated Ki67 indices (often exceeding 20-30%), and these and appear to share similar behaviour and clinical characteristics with well differentiated high grade duodeno-pancreatic NETs (ki-67>20%). Such clinical cases fall into a "grey zone" where treatment prioritization is challenging due to limited data and lack of clear guidelines.

The primary endpoint of this study will be to compare therapeutic algorithm applied to well-differentiated duodeno-pancreatic, thymic and lung NETs with high proliferative indices (Ki-67 > 20%) based on the hypothesis that patients belonging to these distinct groups do not differ significantly from a clinical point of view in terms of diagnosis and treatment management.

Secondarily we will investigate the correlation of genomic alterations with patients' outcome and treatment activity and efficacy.

  • To compare overall survival (OS) in the two groups.
  • To compare first line progression-free survival (PFS) and time to progression (TTP) in the histological groups.
  • To assess treatment response across lines of therapy, including response rate (RR), disease control rate (DCR), and treatment duration in both cohorts.
  • To correlate specific genetic alterations with clinical outcomes (OS, PFS).
  • To explore potential actionable molecular targets and their distribution across the two tumor origins.

Study Type

Observational

Enrollment (Estimated)

34

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Histologically confirmed diagnosis of thymic, pulmonaRy and pancreatic well differentiated high grade neuroendocrine tumors(Ki-67 > 20% according to WHO 2022)

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of well-differentiated high grade neuroendocrine tumor (Ki-67 > 20% according to WHO 2022) performed or reviewed by a NEN-dedicated pathologist.
  • Primary tumor site:thyme, lung and duodenum-pancreas NETs.
  • Advanced stage of tumor disease and Any number of lines of therapy
  • Sufficient available clinical data on diagnosis, treatments, outcomes.

Exclusion Criteria:

  • Poorly differentiated neuroendocrine carcinomas (NECs), GEP NET G1/G2, pulmonary carcinoid with Ki-67 < 20%.
  • Diagnosis of mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs)
  • Inadequate or unavailable tumor tissue for molecular analysis.
  • Incomplete clinical records or follow-up.
  • Other primary sites, except lung or pancreas.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
thymic and pulmonary neuroendocrine neoplasms
thymic and pulmonary well differentiated high grade Advanced stage neuroendocrine tumor
gastroenteropancreatic neuroendocrine neoplasms
gastroenteropancreatic well differentiated high grade neuroendocrine Advanced stage neuroendocrine tumor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutic algorithm
Time Frame: 3 months
The primary endpoint of this study will be to compare therapeutic algorithm applied to the two grups: well-differentiated duodeno-pancreatic, versus thymic and lung NETs with high proliferative indices.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: 3 months
To compare overall survival (OS) in the two groups.
3 months
First line progression-free survival
Time Frame: 3 months
To compare first line progression-free survival (PFS) in the histological groups.
3 months
treatment response across lines of therapy
Time Frame: 3 months
To assess treatment response across lines of therapy, in both cohorts.
3 months
genetic alterations
Time Frame: 3 months
To correlate specific genetic alterations with clinical outcomes (OS, PFS). To explore potential actionable molecular targets and their distribution across the two tumor origins.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Institute of Oncology

Investigators

  • Principal Investigator: Nicola Fazio, MD, IEO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2026

Primary Completion (Estimated)

March 31, 2026

Study Completion (Estimated)

March 31, 2026

Study Registration Dates

First Submitted

February 5, 2026

First Submitted That Met QC Criteria

February 17, 2026

First Posted (Actual)

February 24, 2026

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 17, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • UID 5263
  • L2-518 (Other Identifier: Comitato Etico Territoriale Lombardia 2)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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